Nucleic acids encoding chemokine receptor binding polypeptides

Abstract

The present invention relates to polypeptides directed against or specifically binding to chemokine receptor CXCR2 and in particular to polypeptides capable of modulating signal transduction from CXCR2. The invention also relates to nucleic acids, vectors and host cells capable of expressing the polypeptides of the invention, pharmaceutical compositions comprising the polypeptides and uses of said polypeptides and compositions for treatment of diseases involving aberrant functioning of CXCR2.

The invention claimed is: 
     
       1. An isolated nucleic acid molecule which encodes a polypeptide that binds to the chemokine receptor CXCR2, comprising at least two immunoglobulin antigen binding domains, wherein said polypeptide includes a first antigen binding domain recognising a first epitope on CXCR2 and a second antigen binding domain recognising a second epitope on CXCR2;
 wherein the first antigen binding domain is selected from SEQ ID NO: 213, 214, 216 and 219, and the second antigen binding domain is selected from SEQ ID NO: 215, 217 and 218. 
 
     
     
       2. An expression vector comprising a nucleic acid molecule as claimed in  claim 1 . 
     
     
       3. An isolated ex-vivo host cell comprising the nucleic acid molecule of  claim 1  and capable of expressing the polypeptide encoded by the nucleic acid molecule. 
     
     
       4. The isolated nucleic acid molecule of  claim 1 , wherein the first immunoglobulin single variable domain comprises the amino acid sequence of SEQ ID NO: 216 and the second immunoglobulin single variable domain comprises the amino acid sequence of SEQ ID NO: 217. 
     
     
       5. The isolated nucleic acid molecule of  claim 1 , wherein the polypeptide comprises CDR regions comprising the amino acid sequences of SEQ ID NOs: 141, 236, 181, 146, 237, and 186. 
     
     
       6. The isolated nucleic acid molecule of  claim 1 , wherein the polypeptide comprises the amino acid sequence as set forth in SEQ ID NO: 221. 
     
     
       7. The isolated nucleic acid molecule of  claim 6 , wherein the polypeptide further comprises an HLE binding unit having the amino acid sequence of SEQ ID NO: 228. 
     
     
       8. An isolated nucleic acid molecule of  claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 225.